Genetic Testing for Hypertriglyceridemia in Academic Lipid Clinics: Implications for Precision Medicine-Brief Report.

BACKGROUND: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. METHODS: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight's Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), or very severe (≥1000 mg/dL). RESULTS: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [P=0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. CONCLUSIONS: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.

Behavioral health service use post-jail release and reduced risk of return to jail.

This study examined whether behavioral health service use post-jail release was associated with reduced risk of jail reincarceration. The study sample included 20,615 individuals who had behavioral health diagnoses and were released from the Philadelphia County jail. Using administrative records of the county jail and state-, county-, and Medicaid-funded behavioral health service use from 2010 to 2018, we conducted Cox proportional hazard analyses to estimate the association between behavioral health service use post-jail release and the risk of return to jail within 3 years. Nearly 50% of the sample returned to jail within 3 years. Individuals who used behavioral health services were 26%-38% less likely to return to jail within 3 years than were individuals who did not. The study results suggest that connecting individuals with behavioral health services upon release from jail can reduce the risk of repeated jail incarceration.

Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland.

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. METHODS: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. RESULTS: Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. CONCLUSION: Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.

How Do We Incorporate Polygenic Risk Scores in Cardiovascular Disease Risk Assessment and Management?

PURPOSE OF REVIEW: The potential of polygenic risk scores (PRS) to improve atherosclerotic cardiovascular disease (ASCVD) risk assessment and management has stoked significant interest in their incorporation into clinical management. The goal of this review is to apprise the readers of the latest developments and evidence of PRS readiness for clinical integration. We also discuss current limitations that must be addressed before PRS can be implemented into routine clinical practice. RECENT FINDINGS: PRS have been shown to improve risk stratification for ASCVD and to identify patients who may derive increased benefit from primary and secondary prevention. Risk captured by PRS appears largely independent of traditional risk factors and can be ascertained at birth, prior to the development of traditional clinical risk factors. Genetic risk is modifiable through lifestyle modifications and medications. PRS offers a valuable way to improve early identification of actionable CVD risk. However, further work is needed before PRS can be implemented clinically.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study.

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2-related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2-related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.

Community-academic partnerships in implementation research.

Community-academic partnerships(CAPs) are a critical component of implementing and sustaining evidence-based practices (EBPs) in community settings; however, the approaches used and mechanisms of change within CAPs have not been rigorously studied. The first step to advancing the science of CAP is to operationally define and contextualize the approaches used in CAP as part of the implementation process. Our research group has gleaned valuable lessons about the best ways to develop, support, and nurture community partnerships within the context of implementation. In this article, we share these lessons learned and relate them to implementation strategies that are most relevant to community-partnered implementation endeavors. The implementation strategies most relevant to CAPs are as follows: (a) building a coalition, (b) conducting local consensus discussions, (c) identifying barriers and facilitators to implementation, (d) facilitating interactive problem solving, (e) using an advisory board or workgroup, (f) tailoring strategies, (g) promoting adaptability, and (h) auditing and providing feedback. We offer suggestions for future research to systematically evaluate these strategies, with an eye toward advancing the science of CAP and implementation science and the goal of guiding future research and improving the implementation of EBPs in community settings.

Synchronizing Watches: The Challenge of Aligning Implementation Science and Public Systems.

This special issue of Administration and Policy in Mental Health explores the complexities of the outer system context in implementation science research. In this commentary, we highlight areas of asynchrony between implementation science research and policy realities of public systems. Timing is a critical factor for many aspects of system-level implementation including when and how evidence-based practice initiatives are launched, short and inconsistent timeframes for funding and support, need for early indicators of success and demonstrating return on investment. Greater consideration for the timing that drives change in public systems will strengthen efforts to implement and sustain EBPs in community settings.

Applying the Policy Ecology Framework to Philadelphia's Behavioral Health Transformation Efforts.

Raghavan et al. (Implement Sci 3(26):1-9, 2008) proposed that effective implementation of evidence-based practices requires implementation strategies deployed at multiple levels of the "policy ecology," including the organizational, regulatory or purchaser agency, political, and social levels. However, much of implementation research and practice targets providers without accounting for contextual factors that may influence provider behavior. This paper examines Philadelphia's efforts to work toward an evidence-based and recovery-oriented behavioral health system, and uses the policy ecology framework to illustrate how multifaceted, multilevel implementation strategies can facilitate the widespread implementation of evidence-based practices. Ongoing challenges and implications for research and practice are discussed.

A Multi-Level Examination of Stakeholder Perspectives of Implementation of Evidence-Based Practices in a Large Urban Publicly-Funded Mental Health System.

Our goal was to identify barriers and facilitators to the implementation of evidence-based practices from the perspectives of multiple stakeholders in a large publicly funded mental health system. We completed 56 interviews with three stakeholder groups: treatment developers (n = 7), agency administrators (n = 33), and system leadership (n = 16). The three stakeholder groups converged on the importance of inner (e.g., agency competing resources and demands, therapist educational background) and outer context (e.g., funding) factors as barriers to implementation. Potential threats to implementation and sustainability included the fiscal landscape of community mental health clinics and an evolving workforce. Intervention characteristics were rarely endorsed as barriers. Inner context, outer context, and intervention characteristics were all seen as important facilitators. All stakeholders endorsed the importance of coordinated collaboration across stakeholder groups within the system to successfully implement evidence-based practices.

A Prospective Examination of Clinician and Supervisor Turnover Within the Context of Implementation of Evidence-Based Practices in a Publicly-Funded Mental Health System.

Staff turnover rates in publicly-funded mental health settings are high. We investigated staff and organizational predictors of turnover in a sample of individuals working in an urban public mental health system that has engaged in a system-level effort to implement evidence-based practices. Additionally, we interviewed staff to understand reasons for turnover. Greater staff burnout predicted increased turnover, more openness toward new practices predicted retention, and more professional recognition predicted increased turnover. Staff reported leaving their organizations because of personal, organizational, and financial reasons; just over half of staff that left their organization stayed in the public mental health sector. Implications include an imperative to focus on turnover, with a particular emphasis on ameliorating staff burnout.

Examining the impact of mental illness and substance use on time till re-incarceration in a county jail.

This paper examines the role that substance use and serious mental illness play in criminal justice recidivism by examining the time to return to jail for a cohort of people admitted to jail in 2003 (N = 16,434). These analyses found that people with serious mental illness alone experienced the longest time in the community before returning to jail and were found to have a risk of re-incarceration that did not differ significantly from individuals with no psychiatric or substance use diagnoses. People with co-occurring disorders had a risk of re-incarceration that was over 40 % higher than that of individuals with no diagnosis.

Implementing an E-prescribing system in outpatient mental health programs.

This study describes the implementation and evaluation of an electronic prescription ordering system and feedback report in three community-based mental health outpatient agencies and the usefulness of the system in improving psychiatrists' prescribing behavior. Using the e-prescribing system as a data collection tool, feedback on evidence based prescribing practices for patients diagnosed with schizophrenia spectrum disorder or major affective disorder was provided to agency directors and prescribers via a monthly report. The results of the project were that e-prescribing tools can be installed at a reasonable cost with a short start up period. Although the feedback intervention did not show a significant reduction in questionable prescribing patterns, we should continue to investigate how to best use HIT to improve safety, reduce costs, and enhance the quality of healthcare. A better understanding of what prescribers find useful and the reasons why they are prescribing non-evidenced based medications is needed if interventions of this type are to be effective. Given the availability of administrative claims data and electronic prescribing technology, considerable potential exists to provide useful information for monitoring and clinical decision making in public mental health systems.

Patient and Clinician Perceptions of Precision Cardiology Care: Findings From the HeartCare Study.

BACKGROUND: Routine genome-wide screening for cardiovascular disease risk may inform clinical decision-making. However, little is known about whether clinicians and patients would find such testing useful or acceptable within the context of a genomics-enabled learning health system. METHODS: We conducted surveys with patients and their clinicians who were participating in the HeartCare Study, a precision cardiology care project that returned results from a next-generation sequencing panel of 158 genes associated with cardiovascular disease risk. Six weeks after return of results, we assessed patients' and clinicians' perceived utility and disutility of HeartCare, the effect of the test on clinical recommendations, and patients' attitudes toward integration of research and clinical care. RESULTS: Among 666 HeartCare patients with a result returned during the survey study period, 42.0% completed a full or partial survey. Patient-participants who completed a full survey (n=224) generally had positive perceptions of HeartCare independent of whether they received a positive or negative result. Most patient-participants considered genetic testing for cardiovascular disease risk to have more benefit than risk (88.3%) and agreed that it provided information that they wanted to know (81.2%), while most disagreed that the test caused them to feel confused (77.7%) or overwhelmed (78.0%). For 122 of their patients with positive results, clinicians (n=13) reported making changes in clinical care for 66.4% of patients, recommending changes in health behaviors for 36.9% of patients, and recommending to 33.6% of patients that their family members have clinical testing. CONCLUSIONS: Both patients and clinicians thought the HeartCare panel screen for cardiovascular disease risk provided information that was useful in terms of personal or health benefits to the patient and that informed clinical care without causing patients to be confused or overwhelmed. Further research is needed to assess perceptions of genome-wide screening among the US cardiology clinic population.

Genetic Risk Stratification: A Paradigm Shift in Prevention of Coronary Artery Disease.

Coronary artery disease (CAD) is a pandemic disease that is highly preventable as shown by secondary prevention. Primary prevention is preferred knowing that 50% of the population can expect a cardiac event in their lifetime. Risk stratification for primary prevention using the American Heart Association/American College of Cardiology predicted 10-year risk based on conventional risk factors for CAD is less than optimal. Conventional risk factors such as hypertension, cholesterol, and age are age-dependent and not present until the sixth or seventh decade of life. The genetic risk score (GRS), which is estimated from the recently discovered genetic variants predisposed to CAD, offers a potential solution to this dilemma. The GRS, which is derived from genotyping the population with a microarray containing these genetic risk variants, has indicated that genetic risk stratification based on the GRS is superior to that of conventional risk factors in detecting those at high risk and who would benefit most from statin therapy. Studies performed in >1 million individuals confirmed genetic risk stratification is superior and primarily independent of conventional risk factors. Prospective clinical trials based on risk stratification for CAD using the GRS have shown lifestyle changes, physical activity, and statin therapy are associated with 40% to 50% reduction in cardiac events in the high genetic risk group (20%). Genetic risk stratification has the advantage of being innate to an individual's DNA, and because DNA does not change in a lifetime, it is independent of age. Genetic risk stratification is inexpensive and can be performed worldwide, providing risk analysis at any age and thus has the potential to revolutionize primary prevention.

Artificial Intelligence in Global Health -A Framework and Strategy for Adoption and Sustainability.

Artificial Intelligence (AI) applications in medicine have grown considerably in recent years. AI in the forms of Machine Learning, Natural Language Processing, Expert Systems, Planning and Logistics methods, and Image Processing networks provide great analytical aptitude. While AI methods were first conceptualized for radiology, investigations today are established across all medical specialties. The necessity for proper infrastructure, skilled labor, and access to large, well-organized data sets has kept the majority of medical AI applications in higher-income countries. However, critical technological improvements, such as cloud computing and the near-ubiquity of smartphones, have paved the way for use of medical AI applications in resource-poor areas. Global health initiatives (GHI) have already begun to explore ways to leverage medical AI technologies to detect and mitigate public health inequities. For example, AI tools can help optimize vaccine delivery and community healthcare worker routes, thus enabling limited resources to have a maximal impact. Other promising AI tools have demonstrated an ability to: predict burn healing time from smartphone photos; track regions of socioeconomic disparity combined with environmental trends to predict communicable disease outbreaks; and accurately predict pregnancy complications such as birth asphyxia in low resource settings with limited patient clinical data. In this commentary, we discuss the current state of AI-driven GHI and explore relevant lessons from past technology-centered GHI. Additionally, we propose a conceptual framework to guide the development of sustainable strategies for AI-driven GHI, and we outline areas for future research.

Correction to: A repeated cross-sectional study of clinicians' use of psychotherapy techniques during 5 years of a system-wide effort to implement evidence-based practices in Philadelphia.

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A repeated cross-sectional study of clinicians' use of psychotherapy techniques during 5 years of a system-wide effort to implement evidence-based practices in Philadelphia.

BACKGROUND: Little work investigates the effect of behavioral health system efforts to increase use of evidence-based practices or how organizational characteristics moderate the effect of these efforts. The objective of this study was to investigate clinician practice change in a system encouraging implementation of evidence-based practices over 5 years and how organizational characteristics moderate this effect. We hypothesized that evidence-based techniques would increase over time, whereas use of non-evidence-based techniques would remain static. METHOD: Using a repeated cross-sectional design, data were collected three times from 2013 to 2017 in Philadelphia's public behavioral health system. Clinicians from 20 behavioral health outpatient clinics serving youth were surveyed three times over 5 years (n = 340; overall response rate = 60%). All organizations and clinicians were exposed to system-level support provided by the Evidence-based Practice Innovation Center from 2013 to 2017. Additionally, approximately half of the clinicians participated in city-funded evidence-based practice training initiatives. The main outcome included clinician self-reported use of cognitive-behavioral and psychodynamic techniques measured by the Therapy Procedures Checklist-Family Revised. RESULTS: Clinicians were 80% female and averaged 37.52 years of age (SD = 11.40); there were no significant differences in clinician characteristics across waves (all ps > .05). Controlling for organizational and clinician covariates, average use of CBT techniques increased by 6% from wave 1 (M = 3.18) to wave 3 (M = 3.37, p = .021, d = .29), compared to no change in psychodynamic techniques (p = .570). Each evidence-based practice training initiative in which clinicians participated predicted a 3% increase in CBT use (p = .019) but no change in psychodynamic technique use (p = .709). In organizations with more proficient cultures at baseline, clinicians exhibited greater increases in CBT use compared to organizations with less proficient cultures (8% increase vs. 2% decrease, p = .048). CONCLUSIONS: System implementation of evidence-based practices is associated with modest changes in clinician practice; these effects are moderated by organizational characteristics. Findings identify preliminary targets to improve implementation.

Place and community inclusion: Locational patterns of supportive housing for people with intellectual disability and people with psychiatric disorders.

PURPOSE: This study examines the locational patterns of publicly-funded supportive housing for people with intellectual disability (people with ID) and people with psychiatric disorders (people with PD). METHODS: Administrative data provided housing locations of 4599 people with ID and people with PD in one urban county and one suburban county in the United States. Census tract data captured neighborhood characteristics. Descriptive statistics and spatial analysis were used to analyze the distribution of supportive housing sites. RESULTS: People with ID were more dispersed across a larger number of census tracts with smaller number of residents per tract than people with PD. While spatial dispersion in favor of people with ID was consistent across both counties, difference in dispersion was more pronounced in the urban county. People with PD were concentrated in neighborhoods with more socio-economic disadvantage, more residential instability, and a higher level of race/ethnic diversity than people with ID. CONCLUSION: This study suggests that spatial-analytic method can serve as a useful tool for assessing the extent to which integrated housing is achieved for people with ID and people with PD. Interpretation of findings should be given due consideration of the policy context and neighborhood characteristics of the study communities.

State Adoption of Incentives to Promote Evidence-Based Practices in Behavioral Health Systems.

OBJECTIVE: Despite the critical role behavioral health care payers can play in creating an incentive to use evidence-based practices (EBPs), little research has examined which incentives are used in public mental health systems, the largest providers of mental health care in the United States. METHODS: The authors surveyed state mental health directors from 44 states about whether they used any of seven strategies to increase the use of EBPs. Participants also ranked attributes of each incentive on the basis of key characteristics of diffusion of innovation theory (perceived advantage, simplicity, compatibility, observability, and gradually implementable) and perceived effectiveness. RESULTS: Almost three-quarters of state directors endorsed using at least one financial incentive; most paid for training and technical assistance. Few used other incentives. Strategies perceived as simple and compatible were more readily adopted. Enhanced rates and paying for better outcomes were perceived as the most effective but were the least deployed, suggesting that simplicity and organizational compatibility may be the most decisive factors when choosing incentives. CONCLUSIONS: Payers are not using the incentives they perceive as most effective, and they are mostly using only one strategy for reasons of simplicity and compatibility. Future work should focus on barriers to measurement that likely hinder the adoption and implementation of paying for better outcomes and enhanced reimbursement rates, with the ultimate goal of measuring the effectiveness of incentives on EBP implementation efforts.